Process for the production of methyl methacrylate

Abstract

The present invention relates to a process for the production of methyl methacrylate. The process of the present invention comprises the steps of: a) providing a microorganism in a fermentation medium, under conditions which said microorganism will produce a C3-C12 methacrylate ester; b) providing an organic phase in contact with the fermentation medium, said organic phase including C3-C12 methacrylate ester in a higher concentration than that in the fermentation medium; c) removing organic phase containing the said C3-C12 methacrylate ester from contact with the fermentation medium; and d) transesterifying the removed C3-C12 methacrylate ester with methanol, optionally after separation from the organic phase, to produce methyl methacrylate.

The invention claimed is: 
     
       1. A process for the production of methyl methacrylate (MMA), the process comprising the steps of:
 a) providing a microorganism that expresses one or more enzymes necessary to catalyse the production of C 3 -C 12  methacrylate esters in a fermentation medium, under conditions which said microorganism will produce a C 3 -C 12  methacrylate ester enzymatically; 
 b) providing an organic phase in contact with the fermentation medium, said organic phase including C 3 -C 12  methacrylate ester in a higher concentration than that in the fermentation medium; 
 c) removing organic phase containing said C 3 -C 12  methacrylate ester from contact with the fermentation medium; and 
 d) transesterifying the removed C 3 -C 12  methacrylate ester with methanol, optionally after separation from the organic phase, to produce methyl methacrylate, wherein the transesterification of step d) is non-enzymatic takes place in the presence of methanol and a base catalyst. 
 
     
     
       2. The process according to  claim 1  wherein the methacrylate ester is selected from a C 3 -C 12  alkyl, hydroxyalkyl, alkenyl, alkylaryl or alkenylaryl methacrylate ester. 
     
     
       3. The process according to  claim 1 , wherein the methacrylate ester is selected from n-propyl, isopropyl, isobutyl, n-butyl, t-butyl, isopentyl, hexyl, cyclohexyl, heptyl, octyl, 2-ethylhexyl, decyl, dodecyl, hydroxyethyl, hydroxypropyl, isobornyl, allyl or cinnamyl methacrylate. 
     
     
       4. The process according to  claim 1 , where the microorganism comprises  E. coli, Corynebacterium glutamicum, Pseudomonas fluorescens  or  Pseudomonas putida.    
     
     
       5. The process according to  claim 4 , wherein the microorganism is genetically modified to produce more C 3 -C 12  methacrylate ester than a wild-type microorganism. 
     
     
       6. The process according to  claim 1 , wherein the microorganism expresses one or more enzymes which can convert isobutyryl-CoA to methacrylyl-CoA. 
     
     
       7. The process according to  claim 1 , wherein the microorganism expresses one or more enzymes which can convert methacrylyl-CoA to a C 3 -C 12  methacrylate ester. 
     
     
       8. The process according to  claim 1 , wherein the microorganism expresses an oxidase, dehydrogenase or oxidoreductase enzyme and an alcohol acyltransferase enzyme. 
     
     
       9. The process according to  claim 8 , wherein the oxidase is an acyl CoA oxidase. 
     
     
       10. The process according to  claim 8 , wherein the oxidase is acyl-coenzyme A oxidase  4  (ACX 4) from  Arabidopsis thaliana.    
     
     
       11. The process according to  claim 1 , wherein the microorganism expresses one or more enzymes which can convert 2-ketoisovaleric acid to isobutyryl-CoA. 
     
     
       12. The process according to  claim 11 , wherein the enzyme comprises an oxidoreductase enzyme. 
     
     
       13. The process according to  claim 12 , wherein the oxidoreductase enzyme is a branched chain keto acid dehydrogenase enzyme complex that comprises branched chain keto acid dehydrogenase (BCKD) from  P. putida , BCKD from  Bacillus subtilis , BCKD from  P. aeuruginosa , BCKD from  A. thaliana , BCKD from  Streptomyces coelicolor  or BCKD from  Thermus thermophiles.    
     
     
       14. The process of  claim 1 , wherein the catalyst is selected from metal oxide, hydroxide, carbonate, acetate (ethanoate), oxalate, alkoxide, hydrogencarbonate, a quaternary ammonium compound of one of the above, an alkyl or phenyl amine, diazabicycloundecene and diazabicyclononane. 
     
     
       15. The process of  claim 1 , wherein the catalyst is selected from one or more of the following: LiOH, NaOH, KOH, Mg(OH) 2 , Ca(OH) 2 , Ba(OH) 2 , CsOH, Sr(OH) 2 , RbOH, NH 4 OH, Li 2 CO 3 , Na 2 CO 3 , K 2 CO 3 , Rb 2 CO 3 , Cs 2 CO 3 , MgCO 3 , CaCO 3 , SrCO 3 , BaCO 3 , (NH 4 ) 2 CO 3 , LiHCO 3 , NaHCO 3 , KHCO 3 , RbHCO 3 , CsHCO 3 , Mg(HCO 3 ) 2 , Ca(HCO 3 ) 2 , Sr(HCO 3 ) 2 , Ba(HCO 3 ) 2 , NH 4 HCO 3 , Li 2 O, Na 2 O, K 2 O, Rb 2 O, Cs 2 O, MgO, CaO, SrO, BaO, Li(OR 1 ), Na(OR 1 ), K(OR 1 ), Rb(OR 1 ), Cs(OR 1 ), Mg(OR 1 ) 2 , Ca(OR 1 ) 2 , Sr(OR 1 ) 2 , Ba(OR 1 ) 2 , NH4(OR 1 ) where R 1  is any C1 to C6 branched, unbranched or cyclic alkyl group, being optionally substituted with one or more functional groups; NH 4 (R 2 CO 2 ), Li(R 2 CO 2 ), Na(R 2 CO 2 ), K 2 (R 2 CO 2 ), Rb(R 2 CO 2 ), Cs(R 2 CO 2 ), Mg(R 2 CO 2 ) 2 , Ca(R 2 CO 2 ) 2 , Sr(R 2 CO 2 ) 2  or Ba(R 2 CO 2 ) 2 , where R 2 CO 2  is acetate; (NH 4 ) 2 (CO 2 R 3 CO 2 ), Li 2 (CO 2 R 3 CO 2 ), Na 2 (CO 2 R 3 CO 2 ), K 2 (CO 2 R 3 CO 2 ), Rb 2 (CO 2 R 3 CO 2 ), Cs 2 (CO 2 R 3 CO 2 ), Mg(CO 2 R 3 CO 2 ), Ca(CO 2 R 3 CO 2 ), Sr(CO 2 R 3 CO 2 ), Ba(CO 2 R 3 CO 2 ), (NH 4 ) 2 (CO 2 R 3 CO 2 ), where CO 2 R 3 CO 2  is oxalate; ;
 methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, cyclohexylamine, aniline; R 4 NOH where R is methyl, ethyl propyl, butyl; 
 diazabicycloundecene and diazabicyclononane. 
 
     
     
       16. The process according to  claim 1 , wherein the catalyst is selected from a Group I or Group II metal salt. 
     
     
       17. The process of  claim 1 , wherein the catalyst is selected from Group I or Group II metal oxide, hydroxide, carbonate, acetate, oxalate, alkoxide and hydrogencarbonate. 
     
     
       18. The process according to  claim 1 , wherein the catalyst is a Group I metal salt. 
     
     
       19. The process according to  claim 1 , wherein the catalyst is a Group I methoxide. 
     
     
       20. The process according to  claim 1 , wherein the catalyst is a homogeneous catalyst. 
     
     
       21. The process according to  claim 1 , wherein the catalyst is selected from the group consisting of sodium methoxide, lithium methoxide, potassium methoxide, sodium hydroxide, lithium hydroxide, potassium hydroxide and mixtures thereof. 
     
     
       22. The process according to  claim 1 , wherein the transesterification of step d) takes place in conditions where the mol % water with respect to a catalyst is less than or equal to 50%. 
     
     
       23. The process of  claim 1 , further comprising a step of drying the organic phase wherein the step is carried out prior to the transesterification of step d). 
     
     
       24. The process according to  claim 1 , wherein the transesterification of step d) takes place in the absence of water. 
     
     
       25. The process according to  claim 1 , wherein the titre of C 3 -C 12  methacrylate ester in the fermentation medium is 220 mg/l. 
     
     
       26. The process according to  claim 1 , wherein the organic phase provided in step b) is provided by the C 3 -C 12  methacrylate ester produced by the microorganism. 
     
     
       27. The process according to  claim 1 , wherein the organic phase provided in step b) comprises an external organic solvent in contact with the fermentation medium. 
     
     
       28. The process according to  claim 27 , wherein the organic solvent is biocompatible. 
     
     
       29. The process according to  claim 27 , wherein the organic solvent has a logarithm of octanol/water partition coefficient (logP o/w ) value of greater than or equal to 3.0. 
     
     
       30. The process according to  claim 27 , wherein the solvent is selected from the group consisting of tributyrin, isopropylbenzene, n-propylbenzene, cycloheptane, hexane, heptane, cyclooctane, isooctane, 1,4-diisopropylbenzene, octane, nonane, decane, undecane, dodecane and mixtures thereof. 
     
     
       31. The process according to  claim 1 , further comprising purifying the C 3 -C 12  methacrylate ester in said organic phase. 
     
     
       32. The process according to  claim 12 , wherein the oxidoreductase enzyme is a branched chain keto acid dehydrogenase (BCKD) enzyme complex. 
     
     
       33. The process according to  claim 1 , wherein the microorganism is genetically modified and expresses an exogenous gene encoding an acyl CoA oxidase.